A biochemical feedback signal for hypothermia treatment for neonatal hypoxic-ischemic encephalopathy: focusing on central nervous system proteins in biofluids.

Hypothermia has been widely used to treat moderate to severe neonatal hypoxic-ischemic encephalopathy (HIE), yet evaluating the effects of hypothermia relies on clinical neurology, neuroimaging, amplitude-integrated electroencephalography, and follow-up data on patient outcomes. Biomarkers of brain injury have been considered for estimating the effects of hypothermia. Proteins specific to the central nervous system (CNS) are components of nervous tissue, and once the CNS is damaged, these proteins are released into biofluids (cerebrospinal fluid, blood, urine, tears, saliva), and they can be used as markers of brain damage. Clinical reports have shown that CNS-specific marker proteins (CNSPs) were early expressed in biofluids after brain damage and formed unique biochemical profiles. As a result, these markers may serve as an indicator for screening brain injury in infants, monitoring disease progression, identifying damage region of brain, and assessing the efficacy of neuroprotective measures. In clinical work, we have found that there are few reports on using CNSPs as biological signals in hypothermia for neonatal HIE. The aim of this article is to review the classification, origin, biochemical composition, and physiological function of CNSPs with changes in their expression levels after hypothermia for neonatal HIE. Hopefully, this review will improve the awareness of CNSPs among pediatricians, and encourage future studies exploring the mechanisms behind the effects of hypothermia on these CNSPs, in order to reduce the adverse outcome of neonatal HIE.

Microfluidic sperm sorting selects a subpopulation of high-quality sperm with a higher potential for fertilization.

STUDY QUESTION: Is a microfluidic sperm sorter (MSS) able to select higher quality sperm compared to conventional methods? SUMMARY ANSWER: The MSS selects sperm with improved parameters, lower DNA fragmentation, and higher fertilizing potential. WHAT IS KNOWN ALREADY: To date, the few studies that have compared microfluidics sperm selection with conventional methods have used heterogeneous study population and have lacked molecular investigations. STUDY DESIGN, SIZE, DURATION: The efficiency of a newly designed MSS in isolating high-quality sperm was compared to the density-gradient centrifugation (DGC) and swim-up (SU) methods, using 100 semen samples in two groups, during 2023-2024. PARTICIPANTS/MATERIALS, SETTING, METHODS: Semen specimens from 50 normozoospermic and 50 non-normozoospermic men were sorted using MSS, DGC, and SU methods to compare parameters related to the quality and fertilizing potential of sperm. The fertilizing potential of sperm was determined by measurement of phospholipase C zeta (PLCζ) and post-acrosomal sheath WW domain-binding protein (PAWP) expression using flow cytometry, and the chromatin dispersion test was used to assess sperm DNA damage. MAIN RESULTS AND THE ROLE OF CHANCE: In both normozoospermic and non-normozoospermic groups, the MSS-selected sperm with the highest progressive motility, PLCζ positive expression and PLCζ and PAWP fluorescence intensity the lowest non-progressive motility, and minimal DNA fragmentation, compared to sperm selected by DGC and SU methods (P < 0.05). LIMITATION, REASONS FOR CAUTION: The major limitations of our study were the low yield of sperm in the MSS chips and intentional exclusion of severe male factor infertility to yield a sufficient sperm count for molecular experiments; thus testing with severe oligozoospermic semen and samples with low count and motility is still required. In addition, due to ethical considerations, at present, it was impossible to use the sperm achieved from MSS in the clinic to assess the fertilization rate and further outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Our research presents new evidence that microfluidic sperm sorting may result in the selection of high-quality sperm from raw semen. This novel technology might be a key to improving clinical outcomes of assisted reproduction in infertile patients. STUDY FUNDING/COMPETING INTEREST(S): The study is funded by the Iran University of Medical Sciences and no competing interest exists. TRIAL REGISTRATION NUMBER: N/A.

Comparative Bioinformatic Analysis of the Proteomes of Rabbit and Human Sex Chromosomes.

Studying proteins associated with sex chromosomes can provide insights into sex-specific proteins. Membrane proteins accessible through the cell surface may serve as excellent targets for diagnostic, therapeutic, or even technological purposes, such as sperm sexing technologies. In this context, proteins encoded by sex chromosomes have the potential to become targets for X- or Y-chromosome-bearing spermatozoa. Due to the limited availability of proteomic studies on rabbit spermatozoa and poorly annotated databases for rabbits compared to humans, a bioinformatic analysis of the available rabbit X chromosome proteome (RX), as well as the human X (HX) and Y (HY) chromosomes proteome, was conducted to identify potential targets that could be accessible from the cell surface and predict which of the potential targets identified in humans might also exist in rabbits. We identified 100, 211, and 3 proteins associated with the plasma membrane or cell surface for RX, HX, and HY, respectively, of which 61, 132, and 3 proteins exhibit potential as targets as they were predicted to be accessible from the cell surface. Cross-referencing the potential HX targets with the rabbit proteome revealed an additional 60 proteins with the potential to be RX targets, resulting in a total of 121 potential RX targets. In addition, at least 53 possible common HX and RX targets have been previously identified in human spermatozoa, emphasizing their potential as targets of X-chromosome-bearing spermatozoa. Further proteomic studies on rabbit sperm will be essential to identify and validate the usefulness of these proteins for application in rabbit sperm sorting techniques as targets of X-chromosome-bearing spermatozoa.

Research progress of natural active compounds on improving podocyte function to reduce proteinuria in diabetic kidney disease.

Diabetic kidney disease (DKD) is a primary cause of end-stage renal disease. Proteinuria is a clinical indicator of the different stages of DKD, and podocyte injury is a major cause of proteinuria. Podocyte-specific proteins (PSPs) play important roles in the normal filtration of podocytes. Studies have shown that natural active compounds (NACs) can ameliorate proteinuria; however, the mechanism related to PSPs needs to be explored. In this study, the five stages of DKD related to proteinuria and the functions of PSPs are displayed separately. Mechanisms for ameliorating proteinuria and improving the PSPs of the 15 NACs are summarized. The in vitro and in vivo mechanistic research showed that five compounds, astragaloside IV, ligustrazine, berberine, emodin and resveratrol, exerted renal protective effects via AMPK signaling, icariin and berberine via TLR4 signaling, hirudin and baicalin via MAPK signaling, curcumin and baicalin via NF-κB signaling, and emodin via protein kinase RNA-like endoplasmic reticulum kinase signaling. The 13 PSPs were divided into five categories: actin cytoskeleton, basal domain, apical domain, slit diaphragm, and others. In conclusion, anti-inflammatory effects, anti-oxidative stress, and enhanced autophagy are the main mechanisms underlying the ameliorative effects of NACs. Podocyte apoptosis is mainly related to nephrin and podocin, which are the most studied slit diaphragm PSPs.

In Silico Identification of Potential Quadruplex Forming Sequences in LncRNAs of Cervical Cancer.

Long non-coding RNAs (lncRNAs) have emerged as auxiliary regulators of gene expression influencing tumor microenvironment, metastasis and radio-resistance in cancer. The presence of lncRNA in extracellular fluids makes them promising diagnostic markers. LncRNAs deploy higher-order structures to facilitate a complex range of functions. Among such structures, G-quadruplexes (G4s) can be detected or targeted by small molecular probes to drive theranostic applications. The in vitro identification of G4 formation in lncRNAs can be a tedious and expensive proposition. Bioinformatics-driven strategies can provide comprehensive and economic alternatives in conjunction with suitable experimental validation. We propose a pipeline to identify G4-forming sequences, protein partners and biological functions associated with dysregulated lncRNAs in cervical cancer. We identified 17 lncRNA clusters which possess transcripts that can fold into a G4 structure. We confirmed in vitro G4 formation in the four biologically active isoforms of SNHG20, MEG3, CRNDE and LINP1 by Circular Dichroism spectroscopy and Thioflavin-T-assisted fluorescence spectroscopy and reverse-transcriptase stop assay. Gene expression data demonstrated that these four lncRNAs can be potential prognostic biomarkers of cervical cancer. Two approaches were employed for identifying G4 specific protein partners for these lncRNAs and FMR2 was a potential interacting partner for all four clusters. We report a detailed investigation of G4 formation in lncRNAs that are dysregulated in cervical cancer. LncRNAs MEG3, CRNDE, LINP1 and SNHG20 are shown to influence cervical cancer progression and we report G4 specific protein partners for these lncRNAs. The protein partners and G4s predicted in lncRNAs can be exploited for theranostic objectives.

Cerebrospinal fluid camk2a levels at baseline predict long-term progression in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) remains a highly unpredictable disease. Many hope that fluid biomarkers may contribute to better stratification of disease, aiding the personalisation of treatment decisions, ultimately improving patient outcomes. OBJECTIVE: The objective of this study was to evaluate the predictive value of CSF brain-specific proteins from early in the disease course of MS on long term clinical outcomes. METHODS: In this study, 34 MS patients had their CSF collected and stored within 5 years of disease onset and were then followed clinically for at least 15 years. CSF concentrations of 64 brain-specific proteins were analyzed in the 34 patient CSF, as well as 19 age and sex-matched controls, using a targeted liquid-chromatography tandem mass spectrometry approach. RESULTS: We identified six CSF brain-specific proteins that significantly differentiated MS from controls (p < 0.05) and nine proteins that could predict disease course over the next decade. CAMK2A emerged as a biomarker candidate that could discriminate between MS and controls and could predict long-term disease progression. CONCLUSION: Targeted approaches to identify and quantify biomarkers associated with MS in the CSF may inform on long term MS outcomes. CAMK2A may be one of several candidates, warranting further exploration.

Species-Deconvolved Proteomics for In Situ Investigation of Tumor-Stroma Interactions after Treatment of Pancreatic Cancer Patient-Derived Xenografts with Combined Gemcitabine and Paclitaxel.

Tumor-stroma interactions are critical in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutics. Patient-derived xenograft (PDX) models recapitulate tumor-stroma interactions, but the conventional antibody-based immunoassay is inadequate to discriminate tumor and stromal proteins. Here, we describe a species-deconvolved proteomics approach embedded in IonStar that can unambiguously quantify the tumor (human-derived) and stromal (mouse-derived) proteins in PDX samples, enabling unbiased investigation of tumor and stromal proteomes with excellent quantitative reproducibility. With this strategy, we studied tumor-stroma interactions in PDAC PDXs that responded differently to Gemcitabine combined with nab-Paclitaxel (GEM+PTX) treatment. By analyzing 48 PDX animals 24 h/192 h after treatment with/without GEM+PTX, we quantified 7262 species-specific proteins under stringent cutoff criteria, with high reproducibility. For the PDX sensitive to GEM+PTX, the drug-dysregulated proteins in tumor cells were involved in suppressed oxidative phosphorylation and the TCA cycle, and in the stroma, inhibition of glycolytic activity was predominant, suggesting a relieved reverse Warburg effect by the treatment. In GEM+PTX-resistant PDXs, protein changes suggested extracellular matrix deposition and activation of tumor cell proliferation. Key findings were validated by immunohistochemistry (IHC). Overall, this approach provides a species-deconvolved proteomic platform that could advance cancer therapeutic studies by enabling unbiased exploration of tumor-stroma interactions in the large number of PDX samples required for such investigations.

Germ Cell-Specific Proteins AKAP4 and ASPX Facilitate Identification of Rare Spermatozoa in Non-Obstructive Azoospermia.

Non-obstructive azoospermia (NOA), the most severe form of male infertility, could be treated with intracytoplasmic sperm injection, providing spermatozoa were retrieved with the microdissection testicular sperm extraction (mTESE). We hypothesized that testis-specific and germ cell-specific proteins would facilitate flow cytometry-assisted identification of rare spermatozoa in semen cell pellets of NOA patients, thus enabling non-invasive diagnostics prior to mTESE. Data mining, targeted proteomics, and immunofluorescent microscopy identified and verified a panel of highly testis-specific proteins expressed at the continuum of germ cell differentiation. Late germ cell-specific proteins AKAP4_HUMAN and ASPX_HUMAN (ACRV1 gene) revealed exclusive localization in spermatozoa tails and acrosomes, respectively. A multiplex imaging flow cytometry assay facilitated fast and unambiguous identification of rare but morphologically intact AKAP4+/ASPX+/Hoechst+ spermatozoa within debris-laden semen pellets of NOA patients. While the previously suggested markers for spermatozoa retrieval suffered from low diagnostic specificity, the multistep gating strategy and visualization of AKAP4+/ASPX+/Hoechst+ cells with elongated tails and acrosome-capped nuclei facilitated fast and unambiguous identification of the mature intact spermatozoa. AKAP4+/ASPX+/Hoechst+ assay may emerge as a noninvasive test to predict retrieval of morphologically intact spermatozoa by mTESE, thus improving diagnostics and treatment of severe forms of male infertility.

Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames.

All species continuously evolve short open reading frames (sORFs) that can be templated for protein synthesis and may provide raw materials for evolutionary adaptation. We analyzed the evolutionary origins of 7,264 recently cataloged human sORFs and found that most were evolutionarily young and had emerged de novo. We additionally identified 221 previously missed sORFs potentially translated into peptides of up to 15 amino acids-all of which are smaller than the smallest human microprotein annotated to date. To investigate the bioactivity of sORF-encoded small peptides and young microproteins, we subjected 266 candidates to a mass-spectrometry-based interactome screen with motif resolution. Based on these interactomes and additional cellular assays, we can associate several candidates with mRNA splicing, translational regulation, and endocytosis. Our work provides insights into the evolutionary origins and interaction potential of young and small proteins, thereby helping to elucidate this underexplored territory of the human proteome.

De novo assembled transcriptomics assisted label-free quantitative proteomics analysis reveals sex-specific proteins in the intestinal tissue of Haemaphysalis qinghaiensis.

The hard tick Haemaphysalis qinghaiensis is the vector of a wide variety of infectious agents, such as spirochetes and other bacteria as well as viruses in the western plateau of China. Tick midgut is the key tissue involved in the host-pathogen-vector interface. Multiple midgut proteins are related to key functions in blood digestion, tick survival, and tick-borne pathogen transmission. However, information on the sex-specific proteins expressed in the midgut tissue of H. qinghaiensis for which the genome has not been sequenced is limited. Hence, we assembled and characterized the transcriptome of the H. qinghaiensis midgut and identified the differentially expressed genes (DEGs) in female and male ticks. The sequencing of the mRNA for this nonmodel species is essential for producing a protein database for mass spectrometry-based identification. Here, we combined high-throughput parallel sequencing and label-free quantitative proteomics analysis to extensively characterize the tick midgut using massive RNA sequencing and mass spectrometry, which allowed the detection of genes and proteins. A total of 279,186 transcripts were annotated into 125,790 coding sequences (CDSs), which were manually curated into 96 different gene families. A total of 12,837 DEGs between the two sexes were found by RNA-seq analysis. Of these, 5401 were upregulated genes, while 7436 were downregulated genes. The most common molecular functions were those related to the endocrine system, translation, signal transduction, transport, and catabolism. Meanwhile, the most common biological processes were related to cellular processes, metabolic processes, cellular anatomical entities, and cargo receptor activities. An analysis of the label-free protein quantitation dataset showed 272 upregulated proteins and 46 downregulated proteins when the fold-change was >2.0 (LC-MS/MS). Association analysis of the transcriptome and proteome with GO functional enrichment showed that the majority of the genes (proteins) were those related to catalytic activity, binding, cellular processes, metabolic processes, and responses to stimuli. This study aims to elucidate the digestive physiology of H. qinghaiensis as well as its physiological sexual dimorphism. This will allow the identification of protein candidates with physiological importance that could be used as targets to control the vector as well as the transmission of tick-borne pathogens to humans and animals.

Gene-by-gene screen of the unknown proteins encoded on Plasmodium falciparum chromosome 3.

Taxon-specific proteins are key determinants defining the biology of all organisms and represent prime drug targets in pathogens. However, lacking comparability with proteins in other lineages makes them particularly difficult to study. In malaria parasites, this is exacerbated by technical limitations. Here, we analyzed the cellular location, essentiality, function, and, in selected cases, interactome of all unknown non-secretory proteins encoded on an entire P. falciparum chromosome. The nucleus was the most common localization, indicating that it is a hotspot of parasite-specific biology. More in-depth functional studies with four proteins revealed essential roles in DNA replication and mitosis. The mitosis proteins defined a possible orphan complex and a highly diverged complex needed for spindle-kinetochore connection. Structure-function comparisons indicated that the taxon-specific proteins evolved by different mechanisms. This work demonstrates the feasibility of gene-by-gene screens to elucidate the biology of malaria parasites and reveal critical parasite-specific processes of interest as drug targets.

The Application of Ejaculate-Based Shotgun Proteomics for Male Infertility Screening.

Problems with the male reproductive system are of both medical and social significance. As a rule, spermatozoa and seminal plasma proteomes are investigated separately to assess sperm quality. The current study aimed to compare ejaculate proteomes with spermatozoa and seminal plasma protein profiles regarding the identification of proteins related to fertility scores. A total of 1779, 715, and 2163 proteins were identified in the ejaculate, seminal plasma, and spermatozoa, respectively. Among these datasets, 472 proteins were shared. GO enrichment analysis of the common proteins enabled us to distinguish biological processes such as single fertilization (GO:0007338), spermatid development (GO:0007286), and cell motility (GO:0048870). Among the abundant terms for GO cellular components, zona pellucida receptor complex, sperm fibrous sheath, and outer dense fiber were revealed. Overall, we identified 139 testis-specific proteins. For these proteins, PPI networks that are common in ejaculate, spermatozoa, and seminal plasma were related to the following GO biological processes: cilium movement (GO:0003341), microtubule-based movement (GO:0007018), and sperm motility (GO:0097722). For ejaculate and spermatozoa, they shared 15 common testis-specific proteins with spermatogenesis (GO:0007283) and male gamete generation (GO:0048232). Therefore, we speculated that ejaculate-based proteomics could yield new insights into the peculiar reproductive physiology and spermatozoa function of men and potentially serve as an explanation for male infertility screening.

Age­related differences for expression of the nerve­specific proteins after peripheral nerve injury.

The effects of aging on axon regeneration currently remain unclear. In addition, the up-regulated expression of neurotrophic factors that occurs within one week of peripheral nerve injury has been shown to play an important role in the axon regeneration. To investigate the effects of aging on axon regeneration, the expression of nerve-specific proteins immediately after peripheral nerve injury were compared between young and aged mice. A mouse peripheral nerve injury model was prepared using the sciatic nerve compression method. In each group, Luxol fast blue staining and immunofluorescence staining were performed to assess the degree of Wallerian degeneration in the sciatic nerve, and to evaluate the expression of repressor element 1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), nerve growth factor (NGF), and semaphorin 3A (Sema3A) in the dorsal root ganglion, respectively. Wallerian degeneration was observed in both young and aged mice after peripheral nerve injury. Significant increases were observed in the expression of REST/NRSF (P<0.0001), NT3 (P=0.0279), and Sema3A (P=0.0175) following peripheral nerve injury in young mice, while that of BDNF (P=0.5583) and NGF (P=0.9769) remained unchanged. On the other hand, no significant differences were noted in the expression of these nerve-specific proteins in aged mice. Based on the results of the present study, compensatory changes induced by peripheral nerve injury were initiated by the up-regulated expression of REST/NRSF in young mice, but not in aged mice.

Tissue-Characteristic Expression of Mouse Proteome.

The mouse is a valuable model organism for biomedical research. Here, we established a comprehensive spectral library and the data-independent acquisition-based quantitative proteome maps for 41 mouse organs, including some rarely reported organs such as the cornea, retina, and nine paired organs. The mouse spectral library contained 178,304 peptides from 12,320 proteins, including 1678 proteins not reported in previous mouse spectral libraries. Our data suggested that organs from the nervous system and immune system expressed the most distinct proteome compared with other organs. We also found characteristic protein expression of immune-privileged organs, which may help understanding possible immune rejection after organ transplantation. Each tissue type expressed characteristic high-abundance proteins related to its physiological functions. We also uncovered some tissue-specific proteins which have not been reported previously. The testis expressed highest number of tissue-specific proteins. By comparison of nine paired organs including kidneys, testes, and adrenal glands, we found left organs exhibited higher levels of antioxidant enzymes. We also observed expression asymmetry for proteins related to the apoptotic process, tumor suppression, and organ functions between the left and right sides. This study provides a comprehensive spectral library and a quantitative proteome resource for mouse studies.

Cellular and molecular distribution of thyroid-specific proteins, thyroid-stimulating hormone receptor (TSH-R) and thyroglobulin (TG) in the central nervous system.

The widespread extra-thyroidal localisation of thyroid-specific proteins, thyroid-stimulating hormone receptor (TSH-R) and thyroglobulin (TG), has been well documented. However, more recent years has seen the focus of this research area shift to the distribution of these thyroid-specific proteins, in the central nervous system (CNS). This is largely attributed to the well-known associations between thyroid auto-immunity and neuro-psychiatric disorders. Although these associations have not yet been well defined, there are several studies that demonstrate the presence of TSH-R and TG proteins in CNS regions and its cellular structures. In addition, there is an emerging body of evidence to describe the potential functional roles of these thyroid proteins in various regions of the CNS. In this review, the neural distribution of TSH-R and TG as well as their possible physiological implications in various regions of human and non-human brain is discussed.

Value of brain damage biomarkers in cerebrospinal fluid in neonates with hypoxic-ischemic brain injury.

Hypoxic-ischemic encephalopathy is one of the leading causes of death and neurological disability worldwide. A key issue in neonates with hypoxic-ischemic encephalopathy is accurately establishing the occurrence and severity of brain lesions soon after a perinatal hypoxic-ischemic event. This is crucial to help with prognosis; guide clinical decision-making, including the use of other therapies; and improve family counseling. Neurobiochemical markers may offer a quantitative approximation for estimating the severity of brain damage and identifying infants who have a high risk of further neurological disability. In addition, they should help identify those neonates who would benefit most from the implementation of other neuroprotective and neuroreparative interventions. Despite considerable progress in this area, relatively few studies have been aimed at examining the clinical utility of brain-specific proteins in cerebrospinal fluid, an important opening to characterizing pathological phenomena associated with hypoxic-ischemic brain injury.

Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis.

Vitamin D plays an essential role in prevention and treatment of osteoporosis. Thyroid hormones, in addition to vitamin D, significantly contribute to regulation of bone remodeling cycle and health. There is currently no data about a possible connection between vitamin D treatment and the thyroid in the context of osteoporosis. Middle-aged Wistar rats were divided into: sham operated (SO), orchidectomized (Orx), and cholecalciferol-treated orchidectomized (Orx + Vit. D3; 5 µg/kg b.m./day during three weeks) groups (n = 6/group). Concentration of 25(OH)D in serum of the Orx + Vit. D3 group increased 4 and 3.2 times (p < 0.0001) respectively, compared to Orx and SO group. T4, TSH, and calcitonin in serum remained unaltered. Vit. D3 treatment induced changes in thyroid functional morphology that indicate increased utilization of stored colloid and release of thyroid hormones in comparison with hormone synthesis, to maintain hormonal balance. Increased expression of nuclear VDR (p < 0.05) points to direct, TSH independent action of Vit. D on thyrocytes. Strong CYP24A1 immunostaining in C cells suggests its prominent expression in response to Vit. D in this cell subpopulation in orchidectomized rat model of osteoporosis. The indirect effect of Vit. D on bone, through fine regulation of thyroid function, is small.

Role of Pentacyclic Triterpenoid Acids in the Treatment of Bladder Cancer.

Bladder cancer carries a poor prognosis and has proven resistance to chemotherapy. Pentacyclic Triterpenoid Acids (PTAs) are natural bioactive compounds that have a well-known impact on cancer research because of their cytotoxic and chemopreventive activities. This review focuses on bladder cancer which can no longer be successfully treated by DNA damaging drugs. Unlike most of the existing drugs against bladder cancer, PTAs are non-toxic to normal cells. Collecting findings from both in vitro and in vivo studies, it has been concluded that PTAs may serve as promising agents in future bladder cancer therapy. In this review, the roles of various PTAs in bladder cancer have been explored, and their mechanisms of action in the treatment of bladder cancer have been described. Specific PTAs have been shortlisted from each of the chief skeletons of pentacyclic triterpenoids, which could be effective against bladder cancer because of their mode of action. This review thereby throws light on the multi targets and mechanisms of PTAs, which are responsible for their selective anticancer effects and provides guidelines for further research and development of new natural antitumor compounds.

Enrichment patterns of intrinsic disorder in proteins.

Intrinsically disordered regions in proteins have been shown to be important in protein function. However, not all proteins contain the same amount of intrinsic disorder. The variation in the levels of intrinsic disorder in different types of proteins has been extensively studied over the last two decades. It is now known that the levels of intrinsic disorder vary in proteins across organisms, functions, diseases, and cellular locations. This review consolidates the known trends in the abundance of intrinsic disorder identified in groups of proteins across varying conditions and functions. It also presents new data towards the understanding of intrinsic disorder in cell type-specific proteins. Supplementary Information: The online version contains supplementary material available at 10.1007/s12551-022-01016-7.

Mouse Organ-Specific Proteins and Functions.

Organ-specific proteins (OSPs) possess great medical potential both in clinics and in biomedical research. Applications of them-such as alanine transaminase, aspartate transaminase, and troponins-in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human populations are well known, yet their effects on OSPs are less addressed. Here, we used mice as a model and implemented a breadth study to examine the panorgan proteome for potential variations in organ specificity in different genetic backgrounds. Using reasonable resources, we generated panorgan proteomes of four in-bred mouse strains. The results revealed a large diversity that was more profound among OSPs than among proteomes overall. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ-specific and are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.